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Lip-EPA increases vaccine efficacy by leveraging tumor IDO1 expression, reducing intratumoral IDO mRNA (~fourfold), enhancing infiltrating T lymphocytes and IFN-γ, and modulating regulatory T cells, yielding strong tumor growth delay and improved survival in treated mice.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/targeting-the-tumor-microenvironment-by-liposomal-epacadostat-in-combination-with-liposomal-gp100-vaccine/405523/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/targeting-the-tumor-microenvironment-by-liposomal-epacadostat-in-combination-with-liposomal-gp100-vaccine/405523.png","ImageObject",300,407,{"name":42,"@type":43},"Emma 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decreases intratumoral IDO mRNA, increases infiltrated T lymphocytes, boosts IFN-γ production, and significantly modulates intratumoral regulatory T cells.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},405523,1790716453,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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microenvironment by liposomal Epacadostat in combination with liposomal gp100 vaccine  \nSaharTahaghoghi‑Hajghorbani1,2, Mona Yazdani2, Amin Reza Nikpoor3, Mahdi Hatamipour2, AbolghasemAjami1, Mahmoud Reza Jaafari2,4,5, Ali Badiee2,5* & Alireza Rafiei6*  \nIndoleamine‑2,3‑dioxygenase (IDO1) pathway has vital role in cancer immune escape and its upregulation leads to immunosuppressive environment which is associated with poor prognosis and progression in various cancers like melanoma. Previously, we showed the antitumoral efficacy of nanoliposomal form of Epacadostat (Lip‑EPA), as an IDO1 inhibitor. Herein, we used Lip‑EPA asa combination approach with liposomal gp100 (Lip‑gp100) anti‑cancer vaccine in melanoma model. Here, we showed that B16F10 tumor express IDO1 so using Lip‑EPA will enhance the efficacy of vaccine therapy. The biodistribution of ICG‑labelled liposomal form of EPA showed the remarkable accumulation of drug at tumor site. In an in vivo study, Lip‑EPA enhanced the antitumor efficacy of Lip‑gp100 in which the IDO mRNA expression was decreased (~fourfold) in tumor samples. Also, we identified a significant increase in the number of infiltrated T lymphocytes (p \u003C 0.0001) with enhanced in interferon gamma (IFN‑γ) production (p \u003C 0.0001). Additionally, Lip‑EPA + Lip‑gp100 significantly modulated intratumoral regulatory T cells which altogether resulted in the highest delay in tumor growth (TGD = 56.54%) and increased life span (ILS > 47.36%) in treated mice. Our study demonstrated that novel combination of Lip‑EPA and Lip‑gp100 was effective treatment with capability of being used in further clinical studies.  \nMelanoma is the malignant tumor of melanocytes caused by the accumulation of genetic mutations which lead to improper regulation of cellular pathways1. Depending on the characteristics of the melanoma (location, stage, and genetic characteristics), treatment options may include surgery, chemotherapy, radiotherapy, photodynamic therapy (PDT), and immunotherapy2. While early diagnosis provides the patients with better survival rates, some cases of melanoma remain undiagnosed until late stages. Therefore, the development of new treatments for melanoma is still a priority. The presence of immunosuppressive cells and inhibitory mediators such as the indoleamine deoxygenase (IDO) results in the immunosuppressive nature of the tumor microenvironment inpatients with high stages3–6.  \nIDO is a single-chain oxidoreductase which its increased expression has been associated with decreased immune cell infiltration and increased Treg cell infiltration in tumors7–9. IDO expression has been reported to increase with the progression of melanoma and is considered as an independent prognostic marker for survival in several cancers10. It has been observed that due to IDO inhibition, apoptosis occurs in Treg cells and not in CD8 + T cells, which play a key role in tumor defense11.To date, several IDO inhibitors including 1-methyl-L or D-tryptophan, brasinin and its derivatives (Navoximod (NLG-919), Indoximod, BMS-986205 and Epacadostat (INCB024360) have been investigated in various studies12–14. Epacadostat (EPA / INCB24360) is a reversible inhibitor of indole amine 2,3-dioxygenase-1 (IDO-1) which inhibits IDO-1 by competitive inhibition without interfering with IDO-2 or TDO15, 16. The clinical effects of this compound have been demonstrated by injecting  \n1Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 2Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. 3Department of Immunology, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. 4Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. 5Department of Pharmaceut","cbCaiiXonsrwynPf","https://ap.wps.com/l/cbCaiiXonsrwynPf","pdf",3066066,15,"English","# Background\n## Melanoma and tumor microenvironment\n## IDO1 and immune suppression\n## IDO inhibitors and epacadostat\n# Methods and Rationale\n## Tumor vaccination challenges\n## Nanoparticles and liposomes as delivery systems\n# Key Findings\n## IDO1 expression and vaccine efficacy\n## Tumor-targeted biodistribution\n## Effects on immune infiltration and cytokines\n## Regulatory T cell modulation and survival outcomes","[{\"question\":\"Why target IDO1 in melanoma immunotherapy?\",\"answer\":\"IDO1 upregulation contributes to cancer immune escape by creating an immunosuppressive tumor microenvironment, associated with poor prognosis and progression.\"},{\"question\":\"What combination is tested in this study?\",\"answer\":\"The study combines nanoliposomal Epacadostat (Lip-EPA), an IDO1 inhibitor, with liposomal gp100 (Lip-gp100) as an anti-cancer vaccine in a melanoma model.\"},{\"question\":\"What immune changes are reported after Lip-EPA plus Lip-gp100 treatment?\",\"answer\":\"Treatment decreases intratumoral IDO mRNA, increases infiltrated T lymphocytes, boosts IFN-γ production, and significantly modulates intratumoral regulatory T cells.\"}]","Targeting the tumor microenvironment by liposomal Epacadostat in combination with liposomal gp100 vaccine | PDF",1790560399,38]